As long ago as 1900, Ehrlich proposed that drugs might be guided to the target organ by attaching the drugs to substances which would seek that target organ. The technology to follow up on Ehrlich's suggestion did not exist until monoclonal antibody technology began to appear in the 1970's. For some years now, publications on the targeting of drugs with the aid of antibodies have been regularly appearing. However, as yet, no antibody-conjugated drug is approved for therapeutic use. Chemists and immunologists continue to experiment, seeking a method of making antibody-drug conjugates which will transport the drug reliably to the target organ and release it at the proper time. It has been found, however, that many such conjugates, although comprised of a known drug and an active antibody, are relatively ineffective. Such failures may be caused by chemical damage to the drug or the antibody, or the antibody's failure to release the drug at the right time and place.
The present invention provides a series of vinca drug conjugates linked to antibodies by means of a linker system which gives particularly good release of the drug, in a physiologically active form.